Kistik Fibrozis Hastalığında Belirlenen Aday Mirna’ların Hasta Nazal ve Serum Örneklerinde Analizi

Abstract

Cystic fibrosis is an autosomal recessive disease which is caused by the mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Detection of CFTR mutations ensures the diagnosis but doesn’t give any information about the phenotypic heterogeneity. Recent studies showed that epigenetic mechanisms influence the clinical severity of the diseases. In our preliminary studies, miRNAs that showed statistically significant expression change were determined in severe patients relative to mild patients. Our aim in this thesis is to determine the significantly changing micro RNAs, their potential target genes and related pathways in patients that show different clinical severity despite having the same CFTR mutation. In this thesis, the expressions of miR-449c-5p, miR-34c-3p, miR-34c-5p, and miR-4793-3p were analyzed by Real-time Quantitative Polymerase Chain Reaction from the nasal swab and serum samples from patients with severe and mild disease condition that has the same mutation class. Expression of miR-449c-5p was found to be significantly increasing (2.85-fold) in the nasal swab samples of the severe patients compared to the mild patients (p=0,03). Transport to membrane, vesicular transport, and TGF-beta signaling pathways which are related with cystic fibrosis were identified in the pathway analysis which is performed with miR-449c-5p potential target genes. Also, the expression of miR-449c-5p was found to be significantly decreasing in severe patients which are treated with modulator treatment (Trikafta) compared to non-treated severe patients (p=0,04), and decreasing non-significantly in mild patients which are treated compared to non-treated mild patients. This thesis study may support the development of new biomarker and therapeutic methods for cystic fibrosis and related diseases in the future.